Protective Effects of Low‐Dose Alcohol against Acute Stress‐Induced Renal Injury in Rats: Involvement of CYP4A/20‐HETE and LTB₄/BLT1 Pathways

Abstract

Low-dose alcohol possesses multiple bioactivities. Accordingly, we investigated the protective effect and related molecular mechanism of low-dose alcohol against acute stress- (AS-) induced renal injury. Herein, exhaustive swimming for 15 min combined with restraint stress for 3 h was performed to establish a rat acute stress model, which was verified by an open field test. Evaluation of renal function (blood creatinine and urea nitrogen), urine test (urine leukocyte esterase and urine occult blood), renal histopathology, oxidative stress, inflammation, and apoptosis was performed. The key indicators of the cytochrome P450 (CYP) 4A1/20-hydroxystilbenetetraenoic acid (20-HETE) pathway, cyclooxygenase (COX)/prostaglandin E2 (PGE2) pathway, and leukotriene B4 (LTB4)/leukotriene B4 receptor 1 (BLT1) pathway were measured by real-time PCR and ELISA. We found that low-dose alcohol (0.05 g/kg, i.p.) ameliorated AS-induced renal dysfunction and histological damage. Low-dose alcohol also attenuated AS-induced oxidative stress and inflammation, presenting as reduced malondialdehyde and hydrogen peroxide formation, increased superoxide dismutase and glutathione activity, and decreased myeloperoxidase, interleukin-6, interleukin-1β, and monocyte chemoattractant protein-1 levels ( P < 0.05 ). Moreover, low-dose alcohol alleviated AS-induced apoptosis by downregulating Bax and cleaved caspase 3 protein expression and reduced numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick-end label-positive cells ( P < 0.01 ). Correlation analysis indicated that 20-HETE was strongly correlated with oxidative stress, while LTB4 was strongly correlated with inflammation. Low-dose alcohol inhibited AS-induced increases in CYP4A1, CYP4A2, CYP4A3, CYP4A8, and BLT1 mRNA levels and LTB4 and 20-HETE content ( P < 0.01 ). Interestingly, low-dose alcohol had no effect on COX1 or COX2 mRNA expression or the concentration of PGE2. Furthermore, low-dose alcohol reduced calcium-independent phospholipase A2 mRNA expression, but did not affect secreted phospholipase A2 or cytosolic phospholipase A2 mRNA expression. Together, these results indicate that low-dose alcohol ameliorated AS-induced renal injury by inhibiting CYP4A/20-HETE and LTB4/BLT1 pathways, but not the COX/PGE2 pathway.

Chlorogenic Acid Alleviates Chronic Stress-Induced Duodenal Ferroptosis via the Inhibition of the IL-6/JAK2/STAT3 Signaling Pathway in Rats

“…Longer distances, more rearing times, and higher crossing times indicate higher levels of exploratory behavior. 33 The rats after chronic restraint stress show a less total distance, crossing number, and rearing number in OFT and higher CORT content, which is consistent with preceding studies on the effects of chronic stress. 34 Notably, the chronic stress model is successfully established.…”

“…The number of crossing, rearing number, and the total distance measure the explored ability of experimental animals in new environments. Longer distances, more rearing times, and higher crossing times indicate higher levels of exploratory behavior . The rats after chronic restraint stress show a less total distance, crossing number, and rearing number in OFT and higher CORT content, which is consistent with preceding studies on the effects of chronic stress .…”

Evaluation of Superoxide Dismutase Levels in Rodent Visceral Organs and Tissues After Feeding a Diet Fortified With Chilli for Three Months

“…Interestingly, it was found that a chronic but small amount of alcohol consumption increases the SOD levels [47]; in this study, we found similar results as our dose (80% average 1mL/250 of rat) was even smaller than the one used in the study as mentioned above (0.05g/kg). SOD levels in GC and CAP groups did not increase much.…”